Overseen byRichard Dunne, MD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University of Rochester
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The main purpose of this research study is to determine the maximum tolerable dose (MTD) of SX-682 in combination with nivolumab in patients with metastatic pancreatic ductal adenocarcinoma who have completed at least 16 weeks of first line chemotherapy treatment without evidence of disease progression.
Do I need to stop my current medications for this trial?The trial protocol does not specify if you need to stop your current medications. However, you cannot use other investigational drugs, medications at immunosuppressive doses, or certain botanical preparations within 28 days before starting the study drug. It's best to discuss your current medications with the study team.
What safety data exists for SX-682 + Nivolumab in pancreatic cancer treatment?The safety data for Nivolumab, a PD-1 inhibitor, includes reports of immune-related adverse events (irAEs) such as pancreatitis, colitis, and other immune-related toxicities. These adverse events have been observed in various cancer treatments involving Nivolumab, either alone or in combination with other drugs like ipilimumab. The management of these irAEs often involves corticosteroids or other immunosuppressive treatments like infliximab. However, specific safety data for the combination of SX-682 and Nivolumab in pancreatic cancer is not detailed in the provided research.467914
Is the treatment SX-682 + Nivolumab a promising treatment for pancreatic cancer?Yes, the treatment SX-682 + Nivolumab is promising for pancreatic cancer because it shows potential in increasing the number of active immune cells that can fight the cancer, and it has been well-tolerated in trials. This suggests it could help improve survival rates, although more research is needed to confirm these benefits.811121315
What data supports the idea that SX-682 + Nivolumab for Pancreatic Cancer is an effective treatment?The available research does not provide specific data on the effectiveness of SX-682 + Nivolumab for Pancreatic Cancer. Instead, it focuses on the use of Nivolumab for other types of cancer, such as non-small cell lung cancer and melanoma. In these cases, Nivolumab has shown to improve survival rates and is better tolerated compared to some other treatments. However, without specific data on pancreatic cancer, we cannot conclude its effectiveness for this condition.123510
Eligibility Criteria
This trial is for adults over 18 with metastatic pancreatic ductal adenocarcinoma who've completed at least 16 weeks of first-line chemo without the cancer getting worse. They must be able to perform daily activities (ECOG status 0 or 1) and not have brain metastases, active pneumonitis, recent major surgery, other cancers in the last three years, or use immunosuppressants. Participants need functioning organs and can't be pregnant or breastfeeding.Inclusion Criteria
I am fully active or can carry out light work.
I completed 16 weeks of initial chemotherapy without my cancer getting worse.
My cancer is a type of pancreatic cancer that has spread.
Exclusion Criteria
I have heart disease that limits my daily activities.
I have a history of blood disorders like MDS or MPN.
I had major surgery less than 4 weeks ago.
I am on steroids or other drugs that affect my immune system.
I have not had any cancer, except for treatable local cancers, in the last 3 years.
I have cancer that has spread to my brain or its coverings.
I have a serious heart or brain blood vessel condition.
I am not using herbal treatments for my condition.
I haven't had immunotherapy or experimental drugs in the last 4 weeks.
I have a history of long QT syndrome.
I have lung disease or had lung inflammation treated with steroids.
I have lung inflammation that is not caused by an infection.
I have had Hepatitis B or C.
I have active tuberculosis.
Treatment Details
The study tests SX-682 combined with Nivolumab as a maintenance therapy to find the highest dose patients can tolerate. It's for those whose disease didn't progress after initial chemotherapy. The goal is to see how well they handle this combination treatment and what effects it has on their cancer.
1Treatment groups
Experimental Treatment
Group I: Experimental: SX-682 and NivolumabExperimental Treatment2 Interventions
SX-682 Dose: 25, 50, 100, 200, 400mg BID taken as an oral pill
Nivolumab Dose: 240mg, every 2 weeks via intravenous infusion
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of RochesterRochester, NY
Loading ...
Who is running the clinical trial?
University of RochesterLead Sponsor
Syntrix Biosystems, Inc.Industry Sponsor
Bristol-Myers SquibbIndustry Sponsor
References
Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018]The programmed death (PD)-1 immune checkpoint inhibitor nivolumab (Opdivo(®)) is approved in the USA for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have progression on or after platinum-based chemotherapy and in the EU for the treatment of adults with locally advanced or metastatic NSCLC after prior chemotherapy. In previously-treated patients with advanced nonsquamous NSCLC, overall survival was significantly prolonged and the overall response rate was significantly higher in patients who received intravenous nivolumab 3 mg/kg every 2 weeks versus intravenous docetaxel in the pivotal CheckMate 057 trial. Progression-free survival did not significantly differ between patients receiving nivolumab and those receiving docetaxel. Intravenous nivolumab had a manageable adverse event profile (including immune-mediated adverse events) and was better tolerated than docetaxel in the CheckMate 057 trial. Thus, nivolumab is an important new option for use in previously-treated patients with advanced nonsquamous NSCLC.
Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. [2018]Progress in the treatment of patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) has been limited. An improvement in the understanding of tumor immunosurveillance has resulted in the development of the immune checkpoint inhibitors such as nivolumab. Nivolumab (Opdivo(®)), a human immunoglobulin (Ig)G4 anti-programmed death (PD)-1 monoclonal antibody, was the first PD-1 inhibitor approved in the treatment of patients with advanced stage squamous cell NSCLC following platinum-based chemotherapy. CHECKMATE 017, a randomized phase III study of second-line nivolumab versus docetaxel, significantly improved overall survival (OS), progression-free survival (PFS), patient reported outcomes and the safety and tolerability favored patients treated with nivolumab. The ligand (PD-L1) expression did not predict for outcome. In this paper, we review the role of nivolumab in the treatment of NSCLC with particular attention on recent studies, ongoing combination studies, toxicity profile, current and potential predictive biomarkers.
Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]Nivolumab (Opdivo™) is a novel IgG4 subclass programmed death-1 (PD-1) inhibiting antibody that has demonstrated breakthrough-designation anti-tumor activity. To date, clinical trials of nivolumab and other checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concurrent immunosuppression. However, organ transplant recipients are at high-risk of development of malignancy as a result of suppressed immune surveillance of cancer.
Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. [2022]Nivolumab and pembrolizumab are antibodies against the programmed-death-receptor- 1 (PD-1) which are associated with distinct immune related adverse effects (AEs). This meta-analysis of randomized clinical trials aims to summarize current knowledge regarding the toxicity profile of these agents.
Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. [2022]Nivolumab (Opdivo, Bristol Meyer Squibb, New York, NY) and pembrolizumab (Keytruda, Merck, Kenilworth, NJ) are the first two US Food and Drug Administration (FDA)-approved monoclonal antibodies targeting programmed death-1 (PD-1). Nivolumab and pembrolizumab work by interfering with the interaction between PD-1 and programmed death ligand-1 (PD-L1), whose unimpeded interaction downregulates T cells allowing cancer cells to evade immune surveillance. These drugs have earned a series of FDA approvals for melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), urothelial cancer, classical Hodgkin lymphoma, and renal cell cancer. In this review we will summarize the data for efficacy and toxicity for these two agents. We conclude that they represent two valuable but interchangeable alternatives to target their approved indications. We will discuss how this can help global payers seeking to contain the cost of cancer therapeutics that continues to spiral out of control.
Risk of immune-related adverse events associated with ipilimumab-plus-nivolumab and nivolumab therapy in cancer patients. [2022]The aim of this study was to evaluate the risk of immune-related adverse events (irAEs) among cancer patients receiving nivolumab-plus-ipilimumab therapy and nivolumab monotherapy.
Treatment of Immune Checkpoint Inhibitor Induced Colitis with Infliximab. [2020]Several immunotherapeutic agents function against the T cell immune checkpoint inhibitor pathways thereby reestablishing immune response to elusive malignancies. Namely, the programmed death-1 co-receptor (PD-1) or ligand (PD-L1) and cytotoxic T lymphocyte- associated protein 4 (CTLA-4) are well known checkpoint targets of current FDA approved drugs. Among these drugs nivolumab, an IgG4 anti-PD-1 antibody, and ipilimumab, an anti-CTLA-4 antibody, are used to treat numerous malignancies but carry a large list of potential side effects termed immune-related adverse effects (irAEs). We describe the presentation, clinical course, and resolution of steroid-resistant immune checkpoint inhibitor-induced colitis secondary to administration of these two drugs in a 66-year-old female patient treated with infliximab.
CD137 agonist-based combination immunotherapy enhances activated, effector memory T cells and prolongs survival in pancreatic adenocarcinoma. [2022]Pancreatic ductal adenocarcinoma(PDAC) is resistant to the PD-1/PD-L1 blockade therapy. Previously, the combination of PD-1 blockade and vaccine therapy was shown to have a modest antitumor activity in murine models of PDAC. We used a murine syngeneic model of metastatic PDAC to identify, among multiple T cell modulators tested, which therapeutic agents in combination with the GVAX cancer vaccine and an anti-PD-1 antagonist antibody(αPD-1) are able to improve the survival. We found that an anti-CD137 agonist antibody(αCD137) most significantly improved survival in the mouse PDAC model. Moreover, αPD-1 and αCD137 together in combination with vaccine therapy more significantly increased the expression of costimulatory molecules CD137 and OX40 on CD4+PD-1+ and CD8+PD-1+ T cells comparing to αPD-1 or αCD137, respectively, suggesting that T cell activation within PDACs were enhanced by a synergy of αCD137 and αPD-1. On another hand, αCD137 treatment led to an increase in effector memory T cells independent of αPD-1. Although αCD137 does not increase the cytotoxic effector T cell function, the addition of αCD137 to GVAX+αPD-1 increased expression of IFNγ in EOMES + exhausted tumor-infiltrating T cells. Taken together, this preclinical study established the mechanism of targeting CD137 to enhance effector memory and activated T cells in PDAC. Immunohistochemistry analysis of resected human PDACs following the neo-adjuvant GVAX treatment showed increased levels of CD8+ T cells in those with high levels of CD137 expression, supporting an ongoing clinical trial of testing CD137 as a potential target in treating PDACs that are inflamed with T cells by vaccine therapy.
The Simultaneous Onset of Pancreatitis and Colitis as Immune-related Adverse Events in a Patient Receiving Nivolumab Treatment for Renal Cell Carcinoma. [2022]Immune checkpoint inhibitors (ICIs), which have anti-tumor effects, are currently approved for treatment of several kinds of advanced malignancies. However, with their increasing use, a variety of immune-related adverse events (irAEs) in administered patients have been reported. We herein report a rare case of the simultaneous onset of acute pancreatitis and colitis as irAEs during nivolumab treatment given to a patient with renal cell carcinoma, who then shown marked improvement with corticosteroid therapy.
[EVALUATION OF THE EFFICASY OF THE DRUG OPDIVO (NIVOLUMAB) IN A PATIENT DIAGNOSED WITH UNRESECTABLE SKIN MELANOMA, POSITIVE BRAF MUTATION AND DISEASE DISSEMINATION (CASE REPORT)]. [2021]The case was analyzed for response to nivolumab (Opdivo) monotherapy in a patient with recurrent skin melanoma (10x6x6 cm) and disease dissemination (with multiple lung metastasis), positive for BRAF mutation that followed upon the local therapy (surgical excision) and 6 cycles of adjuvant chemotherapy (at CVD regimen - cisplatin, vinblastine, dacarbazine). Histological results: melanoma. Immunohystochemical: S 100-positive; Melan A - positive; HMB45 - positive, AE1/AE3 - negative, p53 - positive in most cells, vim - positive, ɑ sma - weak in most cells, Ki67 - positive in 20%, BRAFmut, ECOG performance status 1, LDH - 1320 U/L (N
Randomized Phase II Study of Nivolumab With or Without Ipilimumab Combined With Stereotactic Body Radiotherapy for Refractory Metastatic Pancreatic Cancer (CheckPAC). [2023]To evaluate the clinical benefit of nivolumab with or without ipilimumab in combination with stereotactic body radiotherapy (SBRT) in patients with refractory metastatic pancreatic cancer (mPC).
Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial. [2023]Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for pancreatic ductal adenocarcinoma (PDAC). We conducted a randomized phase 2 trial evaluating the efficacy of nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) with gemcitabine/nab-paclitaxel (chemotherapy) in patients with first-line metastatic PDAC ( NCT03214250 ). In 105 patients analyzed for efficacy, the primary endpoint of 1-year overall survival (OS) was met for nivo/chemo (57.7%, P = 0.006 compared to historical 1-year OS of 35%, n = 34) but was not met for sotiga/chemo (48.1%, P = 0.062, n = 36) or sotiga/nivo/chemo (41.3%, P = 0.223, n = 35). Secondary endpoints were progression-free survival, objective response rate, disease control rate, duration of response and safety. Treatment-related adverse event rates were similar across arms. Multi-omic circulating and tumor biomarker analyses identified distinct immune signatures associated with survival for nivo/chemo and sotiga/chemo. Survival after nivo/chemo correlated with a less suppressive tumor microenvironment and higher numbers of activated, antigen-experienced circulating T cells at baseline. Survival after sotiga/chemo correlated with greater intratumoral CD4 T cell infiltration and circulating differentiated CD4 T cells and antigen-presenting cells. A patient subset benefitting from sotiga/nivo/chemo was not identified. Collectively, these analyses suggest potential treatment-specific correlates of efficacy and may enable biomarker-selected patient populations in subsequent PDAC chemoimmunotherapy trials.
Case Report: Nivolumab-Induced Autoimmune Pancreatitis. [2022]Nivolumab is an anti-programmed cell death protein 1 monoclonal antibody. While an effective treatment for a variety of tumors, immune checkpoint inhibitors (ICI) can cause immune-related adverse events such as ICI-pancreatic injury (ICI-PI). Here we present a case of a 60-year-old man with metastatic acral melanoma treated with nivolumab and ipilimumab who developed ICI-PI. Changes in positron emission tomography images preceded symptom onset. However, this case is unique in that the patient presented with cholestatic liver disease. Magnetic resonance cholangiopancreatography showed a dilated extrahepatic bile duct that resolved with steroid therapy, similar to the clinical course of autoimmune pancreatitis. ICI-PI has variable presentations including obstructive jaundice with a clinical course mimicking autoimmune pancreatitis and prompt awareness and treatment of ICI-PI is clinically significant given increasing use of ICIs.
Stuttering as a signal of encephalopathy associated with toripalimab in a pancreatic ductal adenocarcinoma patient: a case report. [2023]Immune checkpoint inhibitor (ICI) combined with chemotherapy has exhibited promising results in small sample studies of pancreatic cancer patients. The efficacy of toripalimab, a programmed cell death protein 1 (PD-1) monoclonal antibody has been explored in the previous studies and it was established that immune-related adverse events (irAEs) associated with administration of this drug deserve proper attention and adequate management.
A platform trial of neoadjuvant and adjuvant antitumor vaccination alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable pancreatic adenocarcinoma. [2023]A neoadjuvant immunotherapy platform clinical trial allows for rapid evaluation of treatment-related changes in tumors and identifying targets to optimize treatment responses. We enrolled patients with resectable pancreatic adenocarcinoma into such a platform trial (NCT02451982) to receive pancreatic cancer GVAX vaccine with low-dose cyclophosphamide alone (Arm A; n = 16), with anti-PD-1 antibody nivolumab (Arm B; n = 14), and with both nivolumab and anti-CD137 agonist antibody urelumab (Arm C; n = 10), respectively. The primary endpoint for Arms A/B - treatment-related change in IL17A expression in vaccine-induced lymphoid aggregates - was previously published. Here, we report the primary endpoint for Arms B/C: treatment-related change in intratumoral CD8+ CD137+ cells and the secondary outcomes including safety, disease-free and overall survivals for all Arms. Treatment with GVAX+nivolumab+urelumab meets the primary endpoint by significantly increasing intratumoral CD8+ CD137+ cells (p = 0.003) compared to GVAX+Nivolumab. All treatments are well-tolerated. Median disease-free and overall survivals, respectively, are 13.90/14.98/33.51 and 23.59/27.01/35.55 months for Arms A/B/C. GVAX+nivolumab+urelumab demonstrates numerically-improved disease-free survival (HR = 0.55, p = 0.242; HR = 0.51, p = 0.173) and overall survival (HR = 0.59, p = 0.377; HR = 0.53, p = 0.279) compared to GVAX and GVAX+nivolumab, respectively, although not statistically significant due to small sample size. Therefore, neoadjuvant and adjuvant GVAX with PD-1 blockade and CD137 agonist antibody therapy is safe, increases intratumoral activated, cytotoxic T cells, and demonstrates a potentially promising efficacy signal in resectable pancreatic adenocarcinoma that warrants further study.